zithromax and Toxoplasmosis--Cerebral

Azithromycin can inhibit the growth of Toxoplasma gondii tachyzoïtes in vitro, but the effect is only observed with prolonged incubation with the drug, reflecting the delayed mode of action of this macrolide on the parasite. Azithromycin is probably acting by inhibition of protein synthesis but the site of action and fixation in the parasite has not been demonstrated. Azithromycin is also effective against intracystic bradyzoïtes in vitro, but long term administration of azithromycin to chronically infected mice failed to reduce the mean number of brain cysts. In models of acute toxoplasmosis, azithromycin was found to have a limited effect on brain infection, whereas parasites were cleared from blood and lungs of infected mice, resulting in a significant protection of treated mice comparatively to untreated controls. When azithromycin is combined with pyrimethamine or sulfadiazine, an additive effect is observed in vitro, and a remarkable synergistic effect is observed in vivo in the treatment of acute toxoplasmosis. Together, these results are in favor of the use of azithromycin in combined therapies for the treatment and/or prophylaxis of toxoplasmosis.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Drug Synergism; Drug Therapy, Combination; Humans; In Vitro Techniques; Lung Diseases, Parasitic; Mice; Pyrimethamine; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Animal; Toxoplasmosis, Cerebral

The preferred therapeutic regimen for Toxoplasma encephalitis (TE) is a combination of pyrimethamine and sulfadiazine, and trimethoprim-sulfamethoxazole (TMP-SMX) plus azithromycin is the widespread alternative therapeutic regimen. The synergistic sulfonamides tablet contains TMP, sulfadiazine, and SMX and hypothetically could be used for TE treatment. This study aimed to compare the efficacy and safety of synergistic sulfonamides plus clindamycin (regimen B) with TMP-SMX plus azithromycin (regimen A) for the treatment of human immunodeficiency virus (HIV) associated TE.. This was an open-labeled, multi-center randomized controlled trial recruited from 11 centers. Each recruited patient was randomly assigned to receive regimen A or regimen B for at least 6 weeks. The overall response was evaluated by assessment of the clinical response of TE-associated clinical features and the radiological response of TE-associated radiological findings. The overall response rate, clinical response rate, radiological response rate, and adverse events were assessed at 2, 6, and 12 weeks. Death events were compared between the two regimens at 6, 12, and 24 weeks.. A total of 91 acquired immunodeficiency syndrome (AIDS)/TE patients were included in the final analysis (44 in regimen A vs . 47 in regimen B). The overall response rate, which refers to the combined clinical and radiological response, was 18.2% (8/44) for regimen A and 21.3% (10/47) for regimen B at week 6. The results of clinical response showed that, in comparison with regimen A, regimen B may perform better with regards to its effect on the relief of clinical manifestations (50.0% [22/44] vs . 70.2% [33/47], P = 0.049). However, no significant differences in radiological response, mortality events, and adverse events were found between the two regimens at week 6.. Synergistic sulfonamides plus clindamycin, as a novel treatment regimen, showed no significantly different efficacy and comparable safety in comparison with the TMP-SMX plus azithromycin regimen. In addition, the regimen containing synergistic sulfonamides may exhibit advantages in terms of clinical symptom alleviation.. ChiCTR.org.cn, ChiCTR1900021195.

Topics: Acquired Immunodeficiency Syndrome; Azithromycin; Clindamycin; Encephalitis; Humans; Sulfadiazine; Sulfanilamide; Sulfonamides; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

The benefits of trimethoprim-sulfamethoxazole (TS) prophylaxis reported for persons living with HIV in Cote d'Ivoire are difficult to extrapolate to sub-Saharan African countries where bacterial resistance to TS is higher and cross-resistance between TS and sulfadoxine-pyrimethamine (SP) may impair SP efficacy for malaria treatment. We conducted a community-based cohort study to measure the incidence of potentially TS-preventable illnesses in Blantyre, Malawi. We found a high incidence of malaria, invasive bacterial infections, and probable bacterial pneumonias but low rates of Pneumocystis jiroveci pneumonia, isosporiasis, and Toxoplasma encephalitis. Most bacterial isolates were resistant to TS but sensitive to azithromycin, a possible alternative to TS. Clinical trials are needed to determine the role of TS or alternative regimens for prophylaxis against secondary infections among people living with HIV in sub-Saharan Africa. These should also assess benefit in patients receiving antiretroviral therapy.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Azithromycin; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Malaria; Malawi; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

A prospective study was conducted to evaluate azithromycin in combination with pyrimethamine for treatment of acute Toxoplasma encephalitis in patients with AIDS. Of the 14 patients given 75 mg pyrimethamine and 500 mg azithromycin daily for four weeks, eight were evaluable for clinical response. Five responded favorably, one had an intermediate response and two an unfavorable response. Of the nine patients evaluable for radiological response, six responded favorably, and three had an intermediate response. Eleven adverse events occurred in nine patients: rash (n = 5), abnormal liver function (n = 2), vomiting (n = 3) and hypoacousia (n = 1). This pilot study suggests that the combination of pyrimethamine and azithromycin may be further investigated and that the optimal dosage of azithromycin has yet to be determined.

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Azithromycin; Drug Administration Schedule; Drug Therapy, Combination; Encephalitis; Female; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Pyrimethamine; Sulfadiazine; Toxoplasmosis, Cerebral

Current standard therapies for toxoplasmic encephalitis often cause severe adverse events. A 57-year-old HIV-positive man in Japan who had toxoplasmic encephalitis but was intolerant to trimethoprim/sulfamethoxazole, pyrimethamine, sulfadiazine, and atovaquone was successfully treated with the combination of clindamycin and azithromycin. This drug combination can be an alternative treatment for this condition.

Topics: Antiprotozoal Agents; Azithromycin; Biomarkers; Clindamycin; Drug Therapy, Combination; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Outcome

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been recognized as the most frequent autoimmune encephalitis in children. Several infectious agents have been implicated in anti-NMDA encephalitis.. A previously healthy immunocompetent 9-year-old girl first presented with seizures, headaches and vomiting. Cerebrospinal fluid and brain magnetic resonance imaging were normal. After one week onset, the patient gradually developed unexplained personality and behavior changes, accompanied by fever and seizures again. Repeated CSF analysis revealed a slightly lymphocytic predominant pleocytosis and positive anti-NMDAR antibody. A variety of pathogenic examinations were negative, except for positive toxoplasma IgM and IgG.. The patient was diagnoses for anti-NMDA encephalitis associated with acute acquired toxoplasma gondii infection.. The patient received 10 days azithromycin for treatment of acquired toxoplasma infection. The parents refuse immunotherapy because substantial recovery from clinical symptoms.. The patient was substantially recovered with residual mild agitation after therapy for acquired toxoplasma gondii infection. Two months later, the patient was completely devoid of symptoms, and the levels of serum IgM and IgG of toxoplasma gondii were decreased.. Acquired toxoplasma gondii infection may trigger anti-NMDAR encephalitis in children, which has not been reported previously. Clinicians should assess the possibility of toxoplasma gondii infection when evaluating a patient with anti-NMDA encephalitis.

Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antiprotozoal Agents; Azithromycin; Child; Female; Humans; Immunoglobulin G; Immunoglobulin M; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Outcome

We report one case of successful treatment of cerebral toxoplasmosis in acquired immunodeficiency syndrome (AIDS) with azithromycin combined with pyrimethamine. Toxoplasmic encephalitis had been diagnosed on the basis of multiple lesions exhibiting ring like contrast enhancement on double contrast Computed Tomographic (CT) scan of the brain. Thereby our patient had been treated with pyrimethamine 25 mg/die, after an attack dose of 100 mg in the first day, and clindamycin 2400 mg/die, because of sulfa-drug allergy, but clindamycin had to be discontinued because of rash development. At this point azithromycin, at a dose of 1000 mg/die for 21 days and 1500 mg a week for the following 50 days of follow-up, was added to pyrimethamine. Follow-up CT scan after 20 days of treatment (10 with clindamycin+pyrimethamine and 10 with azithromycin+pyrimethamine) revealed partial resolution of the brain lesions and subsequently (after 50 and 80 days of treatment) complete resolution.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Drug Therapy, Combination; Humans; Male; Middle Aged; Pyrimethamine; Toxoplasmosis, Cerebral

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Humans; Male; Recurrence; Toxoplasmosis, Cerebral

Nineteen cases of cerebral toxoplasmosis (CTOX) are reported from a group of Edinburgh AIDS patients. All patients were severely immunodeficient at the time of presentation with CD4 count < 50 cells/mm3. Thirteen patients had suffered a previous AIDS-defining illness. In Edinburgh, CTOX has developed in 48% of patients who are seropositive for toxoplasma and have a CD4 count < 50 cells/mm3. It is estimated that at least half of the toxoplasma seropositive patients will develop CTOX if they survive for 21 months after reaching a time in their illness when the CD4 count = 50 cells/mm3. The incidence of CTOX in toxoplasma-seronegative patients with a CD4 count < 50 cells/mm3 is 1.3%. All patients showed improvement on treatment and there was no correlation between clinical or radiological features and patient survival. Those patients unable to tolerate first choice anti-toxoplasma therapy had a significantly shorter survival than the remainder but there was no single therapeutic regimen which conferred a survival advantage. Eighteen patients had died at the time of study and the median survival following diagnosis of cerebral toxoplasmosis was 10 months (range 3-38 months). Postmortem examination of the brain was available in 8, 4 of whom had concomitant cerebral lymphoma. The survival from AIDS or CD4 count = 50 cells/mm3 did not differ significantly between those with treated CTOX and a control group who had no toxoplasma infection, suggesting that treatment is reasonably effective. CTOX is a disease associated with severe HIV-related immunodeficiency and, in those with a CD4 count < 50 cells/mm3, occurs more than 35 times as frequently in toxoplasma-seropositive than toxoplasma-seronegative patients. Treatment is effective but the outcome of treated disease cannot be predicted from presenting clinical or radiological features. Concomitant space-occupying cerebral pathology is evident in 50% of post-mortem examinations.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Atovaquone; Autopsy; Azithromycin; Brain; CD4 Lymphocyte Count; Clindamycin; Drug Therapy, Combination; Female; Humans; Incidence; Lymphoma, AIDS-Related; Male; Middle Aged; Naphthoquinones; Pyrimethamine; Retrospective Studies; Sulfadiazine; Toxoplasmosis, Cerebral; United Kingdom

We present a patient with AIDS and toxoplasma encephalitis who was unable to tolerate established therapy with sulphadiazine or clindamycin but responded to oral azithromycin and pyrimethamine. The patient was maintained on oral azithromycin but subsequently relapsed after 8 months. The recurrence was successfully treated with intravenous azithromycin. The case illustrates that azithromycin can be used to treat patients with toxoplasma encephalitis who are unable to tolerate or fail to respond to other therapeutic agents. Failure of oral azithromycin may be due to inadequate tissue concentrations and patients may further benefit from intravenous administration.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Encephalitis; Humans; Infusions, Intravenous; Male; Toxoplasmosis, Cerebral

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Cryptosporidiosis; Humans; Injections, Intravenous; Malaria, Falciparum; Mycobacterium avium-intracellulare Infection; Plasmodium falciparum; Pneumonia; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral

Topics: Adult; AIDS-Related Opportunistic Infections; Azithromycin; Humans; Magnetic Resonance Imaging; Male; Toxoplasmosis, Cerebral

Topics: Adult; AIDS-Related Opportunistic Infections; Azithromycin; Erythromycin; Humans; Male; Toxoplasmosis, Cerebral

Topics: Acquired Immunodeficiency Syndrome; Adult; Azithromycin; Erythromycin; Humans; Male; Toxoplasmosis, Cerebral